Effect of ammonium chloride and dietary phosphorus in the azotaemic rat. I. Renal function and biochemical changes.

BACKGROUND: Both dietary phosphorus restriction and the ingestion of ammonium chloride (NH(4)Cl) given to rats on a high-phosphorus diet have been shown to preserve renal function in the azotaemic rat. Parathyroidectomy also has been reported to preserve renal function and, in addition, to prevent kidney hypertrophy in the remnant kidney model. Our goals were (i) to evaluate in azotaemic rats the effect of dietary phosphorus on renal function in a shorter time frame than previously studied and (ii) to determine whether NH(4)Cl administration (a) enhances the renoprotective effect of dietary phosphorus restriction and (b) improves renal function in the absence of parathyroid hormone (PTH). METHODS: High (H; 1.2%), normal (N; 0.6%) and low (L; <0.05%) phosphorus diets (PD) were given for 30 days to 5/6 nephrectomized rats. In each dietary group, one-half of the rats were given NH(4)Cl in the drinking water. The six groups were HPD + NH(4)Cl, HPD, NPD + NH(4)Cl, NPD, LPD + NH(4)Cl and LPD. The effect of NH(4)Cl administration was also evaluated in 5/6 nephrectomized, parathyroidectomized (PTX) rats on NPD. RESULTS: In each of the three dietary phosphorus groups, creatinine and urea clearances were greater (P<0.01) in rats receiving NH(4)Cl. Neither creatinine nor urea clearance was reduced by high dietary phosphorus. Urine calcium excretion was greatest in the LPD group and was increased (P < or = 0.001) in all three groups by NH(4)Cl ingestion. An inverse correlation was present between plasma calcium and phosphorus in the parathyroid intact (r = -0.79, P<0.001) and PTX groups (r = -0.46, P = 0.02). In PTX rats, NH(4)Cl ingestion increased (P < or = 0.01) creatinine and urea clearances and both an increasing plasma calcium concentration (r = 0.67, P<0.001) and urine calcium excretion (r = 0.73, P<0.001) increased urine phosphorus excretion. CONCLUSIONS: At 30 days of renal failure (i) NH(4)Cl ingestion increased creatinine and urea clearances, irrespective of dietary phosphorus; (ii) high urine calcium excretion, induced by dietary phosphorus restriction and NH(4)Cl ingestion, did not adversely affect renal function; (iii) high dietary phosphorus did not decrease renal function; (iv) the absence of PTH did not preserve renal function or prevent NH(4)Cl from improving renal function; and (v) both an increasing plasma calcium concentration and urine calcium excretion resulted in an increase in urine phosphorus excretion in PTX rats.     

Effect of dietary calcium on stone forming propensity

PURPOSE: Epidemiological studies have reported that high calcium diet protects against kidney stone formation in normal subjects. This metabolic study was designed to elucidate the physiological and physicochemical effects conferring this apparent protection. MATERIALS AND METHODS: A total of 21 normal volunteers underwent 2 phases of study in a crossover, randomized design, wherein they consumed constant metabolic diets that matched the estimated highest and lowest quintiles of calcium intake from published epidemiological studies. RESULTS: Urinary calcium was significantly greater on the high calcium diet (148 +/- 55 versus 118 +/- 43 mg. daily, p <0.01, p <0.01) but urinary oxalate did not differ between diets. There was no difference in relative saturation ratio of calcium oxalate between the 2 diets. The high calcium diet significantly increased saturation of brushite and decreased that of uric acid. Due to the other differences between the diets (more fluid, potassium, magnesium and phosphate in the high calcium diet), the high calcium diet also increased 24-hour urinary volume, potassium, phosphorus, pH and citrate. After adjustment of these confounding variables, the high calcium diet significantly increased relative saturation ratio of calcium oxalate by 24%. CONCLUSIONS: High calcium diet from published epidemiological studies does not alter the propensity for calcium oxalate crystallization in normal subjects despite increased urinary calcium and unaltered urinary oxalate because of the greater amounts of ingested fluid, potassium and phosphate. However, high calcium intake alone, without concomitant changes in the diet, poses a modest risk for calcium stone formation.     

4种大鼠肾草酸钙结石模型的比较

目的筛选简便、快捷、成石效果好的SD大鼠肾草酸钙结石的造模方法。方法分别采用目前普遍使用的2种大鼠肾草酸钙结石的模型复制方法和2种改良的造模方法进行造模,并设立空白对照组,造模结束后采集每组大鼠24h尿量及血清,比较大鼠24h尿量、尿Ca2＋、尿Mg2＋、尿pH、尿草酸（0x）及血尿素氮（BUN）、肌酐（cr）、P、Ca2＋、Mg2＋,肾脏病理切片HE染色后光学显微镜下观察和比较各组大鼠肾脏病理改变及草酸钙结晶的沉积情况。结果E组[1％乙二醇＋2％氯化铵＋10％葡萄糖（48d）]在光学显微镜下草酸钙结晶沉积较传统组C组明显增多（P〈0．05）,但有30％大鼠死亡,血肌酐在5组大鼠中最高。D组[1％乙二醇＋2％氯化铵＋10％葡萄糖（28d）]较传统组C组草酸钙结晶沉积明显增多（P〈0．05）,并且造模时间短,大鼠存活率高（80％）,E组与D组相比结晶形成量无统计学意义（P〉0．05）,B组[1％乙二醇（28d）3肾脏中无肾结晶形成,仅有轻微的肾脏病理学改变,大鼠无死亡,肌酐不高。空白对照组无结晶形成,无病理改变。结论用1％乙二醇＋2％氯化铵＋10％葡萄糖诱导28天复制肾草酸钙结石模型的效果好,并且花费时间短,大鼠存活率高,建议选用。     

Effect of aluminium on the development of hyperparathyroidism and bone disease in the azotaemic rat

Aluminium toxicity in dialysis patients is associated with arelative parathyroid hormone (PTH) deficiency as well as osteomalacia.In-vitro studies of parathyroid cells have shown that aluminiuminhibits PTH secretion. However, only limited data are availableon how aluminium affects the development of hyperparathyroidismin the azotaemic animal. Four groups of azotaemic rats werestudied; in each group, renal failure was induced by a two-stage5/6 nephrectomy, after which rats were studied for 40 days.In three groups hyperparathyroidism was stimulated by the useof a high phosphorus (1.2%) diet (HPD). The four groups were(1) HPD; (2) HPD+high-dose aluminium (HDAL)—1.5 mg ofaluminium was adminis tered intraperitoneally (IP) 5 days perweek; (3) HPD+low-dose aluminium (LDAL)—0.5 mg of aluminiumwas administered IP 5 days per week; and (4) moderate phosphorus(0.6%) diet (MPD); the MPD group was used to control hyperparathyroidismand thus provide a comparison of PTH levels and azota emic bonedisease. After 40 days, the serum PTH level was higher (P<0.05)in the HPD+HDAL group (37±2pmol/l) than the HPD, HPD+LDAL,and MPD groups (24±3, 28±4, and 6±1 pmol/lrespect ively). The correlation between serum PTH and calcium,serum PTH and phosphorus, and serum calcium and phosphorus wassignificant for the four groups (P<0.02); however, the relationshipbetween serum PTH and calcium, and between serum calcium andphosphorus was altered in the HPD+HDAL group (serum aluminium30.8±2µmol/l). Aluminium administration induceda decrease (P<0.05) in the bone formation rate and the adjustedapposition rate, and an increase (P<0.05) in osteoid volumeand the min eralization lag time. Despite aluminium administration,diet-induced hyperparathyroidism resulted in an increase (P<0.05)in the osteoblast surface. In conclusion, in the azotaemic rat(1) aluminium did not slow the development nor decrease themagnitude of hyper parathyroidism; (2) aluminium appeared toalter the relationship between serum PTH and calcium, and betweenserum calcium and phosphorus; (3) hyperpara thyroidism changedthe expression of aluminium-induced bone disease and may affordthe bone some protection against the toxic effects of aluminium.     

The interaction of PTH and dietary phosphorus and calcium on serum calcitriol levels in the rat with experimental renal failure

BACKGROUND.: Renal failure results in decreased calcitriol production, akey factor in the development of secondary hyperparathyroidism.Phosphorus accumulation and high parathyroid hormone (PTH) levels,both inherent to renal failure, have different effects on calcitriolproduction; moreover, dietary calcium loading may have a separateinhibitory effect on calcitriol production. This study was designedto evaluate the relative effects of PTH and dietary phosphorusand calcium on serum calcitriol levels. METHODS.: Renal failure was surgically induced and rats were divided intonormal, moderate renal failure, and advanced renal failure basedon the serum creatinine. Each group was subdivided and receivedeither a highphosphorusdiet (HPD, 0.6% Ca, 1.2% P) or highcalcium diet (HCaD, 1.2% Ca, 0.6% P) for 14–16 days to determinethe relative effects of dietary calcium andphosphorus loadingon serum calcitriol. In addition the effect of PTH and phosphoruson calcitriol stimulation was determined with a 48-h PTH infusioncombined with either a low (0.16%) or high (1%) phosphorus dietsboth diets had negligible calcium (<0.05%) RESULTS.: With decreasing renal function, PTH increased and was greaterin rats fed the HPD than the HCaD; serum calcitriol decreasedas renal function decreased and was lower in normal rats andrats with moderate renal failure fed a HCaD (P < 0.01). Thecalcitriol response to a PTH infusion decreased as renal functiondecreased (P <0.05) but was greater on a low- (0.16%) thana high- (1%) phosphorus diet (P<0.05) CONCLUSION.: Dietary calcium loading either directly decreases serum calcitriolor acts by modifying the stimulatory effect of PTH; the stimulatoryeffect of PTH on serum calcitriol is modified by dietary phosphorus;in moderate renal failure, serum calcitriol levels depend ona complex interaction between PTH and dietary calcium and phosphorus;and in advanced renal failure, serum calcitriol levels are lowand are difficult to stimulate, presumably because of the lossof renal mass.     

Dominant factors of the phosphorus regulatory network differ under various dietary phosphate loads in healthy individuals

BackgroundThe purpose of this study was to explore the contribution of each factor of the phosphorus metabolism network following phosphorus diet intervention via Granger causality analysis.MethodsIn this study, a total of six healthy male volunteers were enrolled. All participants sequentially received regular, low-, and high-phosphorus diets. Consumption of each diet lasted for five days, with a 5-day washout period between different diets. Blood and urinary samples were collected on the fifth day of consumption of each diet at 9 time points (00:00, 04:00, 08:00, 10:00, 12:00, 14:00, 16:00, 20:00, 24:00) for measurements of serum levels of phosphate, calcium, PTH, FGF23, BALP, α-Klotho, and 1,25 D and urinary phosphorus excretion. Granger causality and the centrality of the above variables in the phosphorus network were analyzed by pairwise panel Granger causality analysis using the time-series data.ResultsThe mean age of the participants was 28.5 ± 2.1 years. By using Granger causality analysis, we found that the α-Klotho level had the strongest connection with and played a key role in influencing the other variables. In addition, urinary phosphorus excretion was frequently regulated by other variables in the network of phosphorus metabolism following a regular phosphorus diet. After low-phosphorus diet intervention, serum phosphate affected the other factors the most, and the 1,25 D level was the main outcome factor, while urinary phosphorus excretion was the most strongly associated variable in the network of phosphorus metabolism. After high-phosphorus diet intervention, FGF23 and 1,25 D played a more critical role in active regulation and passive regulation in the Granger causality analysis.ConclusionsVariations in dietary phosphorus intake led to changes in the central factors involved in phosphorus metabolism.     

Effect of dietary phosphate on Na+-dependent phosphate cotransporters function and expression in the rat kidney

Background Three types (typeI, II, andIII) of sodium-dependent phosphate cotransporters have recently been isolated and shown to be expressed in the mammalian kidney. Understanding of the functional roles and regulation of each transporter is still fragmented, however. Methods We analyzed the functional roles of each transporter by using antisense oligonucleotides in theXenopus oocytes expression system, and by localization in the proximal tubules of rat kidney using immunohistochemistry. Results Phosphate uptake in brush border membranes was increased by about 2 times in rats fed a low-phosphate, as compared with a high-phosphate, diet. Expression of typeI, II, andIII transporter mRNAs was observed in renal poly(A)⁺RNA, isolated from the rats fed a low-phosphate diet. Phosphate uptake increased about 2.5-fold inXenopus oocytes injected with the poly(A)⁺RNA, compared with those given RNA from rats fed a high-phosphate diet. Hybrid depletion of the typeII sodium-dependent phosphate transporter (NaPi-2), but not of the typeI (rNaPi-1) or typeIII transporters (PiT-1 and PiT-2), significantly decreased phosphate transport activity in oocytes injected with the poly(A)⁺RNA from each experimental group rat kidney. In rats fed the lowphosphate diet, NaPi-2 immunoreactivity increased markedly in the brush border membranes of renal proximal tubular cells, whereas rNaPi-1 protein was not changed. Conclusion This study suggests that the typeII transporter functions mainly as a sodium-dependent phosphate cotransporter, and is regulated by dietary phosphate in the rat kidney.     

Relationship between dietary phosphorus intake and nutritional status and calcium and phosphorus metabolism in patients with chronic kidney disease

Objective To evaluate the dietary phosphorus intake of non-dialysis patients with chronic kidney disease (CKD) 3-5 stage, and to explore the relationship between dietary phosphorus intake, nutritional status, and calcium and phosphorus metabolism. Methods A cross-sectional study was conducted. Non-dialysis patients of CKD 3-5 stage in Huashan Hospital outpatient clinic were selected. Three-day dietary diaries, anthropometric indicators, subjective global assessment (SGA) scores, blood and 24-hour urine biochemical indicators were collected. According to the median dietary phosphorus intake (873 mg/d), the patients were divided into high phosphorus intake group (≥ 873 mg/d) and low phosphorus intake group (＜873 mg/d). The differences of characteristics, anthropometric indicators, SGA scores, blood and urine biochemical indicators between the two groups were compared. Multivariate linear regression analysis was used to analyze the correlation between dietary phosphorus intake and different kinds of food intake. Results A total of 118 patients were enrolled. The daily energy intake was (25.48±4.45) kcal/kg, protein intake was (0.88±0.22) g/kg and phosphorus intake was (862.85±233.02) mg/d. There were no significant differences in body mass index and SGA scores between high phosphorus intake group and low phosphorus intake group. The waist circumference, hip circumference, waist-hip ratio and leg circumference of male patients in high phosphorus intake group were higher than those in low phosphorus intake group (all P＜0.05). There were no significant differences in anthropometric indicators between the two groups of female patients. The serum levels of intact parathyroid hormone (iPTH), sodium, triglyceride, blood RBC count, alanine aminotransferase, 24-hour urine urea nitrogen, 24-hour urine creatinine and 24-hour urine phosphate in the high phosphorus intake group were higher than those in the low phosphorus intake group (all P＜0.05). Multivariate regression analysis showed that pork and chicken contributed the most to dietary phosphorus intake, followed by fish and dairy. Conclusions The daily dietary phosphorus intake of non-dialysis of CKD 3-5 stage patients is slightly higher than the recommended intake. The increase of dietary phosphorus intake may lead to the increase of serum iPTH and sodium levels. Proper control of dietary phosphorus intake will not impair the nutritional status of CKD patients.     

A systematic review of urinary bladder hypertrophy in experimental diabetes: Part I. Streptozotocin‐induced rat models

Aims

To better understand the genesis and consequences of urinary bladder hypertrophy in animal models of diabetes. This part of a three‐article series will analyze urinary bladder hypertrophy in the diabetes mellitus type 1 model of rats injected with streptozotocin (STZ).

Methods

A systematic search for the key word combination “diabetes,” “bladder” and “hypertrophy” was performed in PubMed; additional references were identified from reference lists of those publications. All papers were systematically extracted for relevant information.

Results

A total of 39 studies were identified that quantitatively reported on bladder hypertrophy in rats upon injection of STZ; of which several reported on multiple time points yielding a total of 83 group comparisons. Bladder hypertrophy was found consistently, being fully developed as early as 1 week after STZ injection (bladder weight 188 ± 59% of matched control). Hypertrophy was similar across sexes and STZ doses (35‐40 vs 50‐65 mg/kg) but appeared greater with Wistar rats than other rat strains. The extent of bladder hypertrophy was not correlated to blood glucose concentrations, but normalization of blood glucose concentration by insulin treatment starting early after STZ injection prevented hypertrophy; insulin treatment starting after hypertrophy had established largely reversed it.

Conclusions

Bladder size approximately doubles after STZ injection in rats; the extent of hypertrophy is not linked to the severity of hyperglycemia but largely reversible by restoration of euglycemia.     

Acute effects of dietary phosphorus intake on markers of mineral metabolism in hemodialysis patients: post hoc analysis of a randomized crossover trial

BackgroundLong-term dietary phosphorus excess influences disturbances in mineral metabolism, but it is unclear how rapidly the mineral metabolism responds to short-term dietary change in dialysis populations.MethodsThis was a post hoc analysis of a randomized crossover trial that evaluated the short-term effects of low-phosphorus diets on mineral parameters in hemodialysis patients. Within a 9-day period, we obtained a total of 4 repeated measurements for each participant regarding dietary intake parameters, including calorie, phosphorus, and calcium intake, and markers of mineral metabolism, including phosphate, calcium, intact parathyroid hormone (iPTH), intact fibroblast growth factor 23 (iFGF23), and C-terminal fibroblast growth factor 23 (cFGF23). The correlations between dietary phosphorus intake and serum mineral parameters were assessed by using mixed-effects models.ResultsThirty-four patients were analyzed. In the fully adjusted model, we found that an increase in dietary phosphorus intake of 100 mg was associated with an increase in serum phosphate of 0.3 mg/dL (95% confidence intervals [CI], 0.2–0.4, p < .001), a decrease in serum calcium of 0.06 mg/dL (95% CI, −0.11 to −0.01, p = .01), an increase in iPTH of 5.4% (95% CI, 1.4–9.3, p = .01), and an increase in iFGF23 of 5.0% (95% CI, 2.0–8.0, p = .001). Dietary phosphorus intake was not related to cFGF23.ConclusionsIncreased dietary phosphorus intake acutely increases serum phosphate, iPTH, and iFGF23 levels and decreases serum calcium levels, highlighting the important role of daily fluctuations of dietary habits in disturbed mineral homeostasis in hemodialysis patients.     

Glomerular hyperfiltration and hypertrophy in the rat hypoplastic kidney as a model of oligomeganephronic disease.

BACKGROUND: Rat male hypogonadisim (hgn/hgn) is accompanied by bilateral hypoplastic kidney (HPK). The HPK contains a reduced number of nephrons that progress to chronic renal failure. In this study, we describe the renal pathophysiology in adult HPK rats as a potential model of oligomeganephronic disease. METHODS: Urine and blood samples were collected from adult male HPK rats and phenotypically normal littermates at 70 days of age for measurements of urea-nitrogen and creatinine clearances (Cun and Ccr). Glomerular number (GN) and glomerular projective area were determined using the maceration method. Blood pressure was measured. Urinary protein and renal histology were examined. Urinary albumin concentration was determined at early postnatal ages. RESULTS: Renal weight was significantly smaller in adult HPK males than in normal males. Polyuria and polydipsia were observed in HPK rats. Ccr and Cun were low in HPK rats compared with those in normal rats. The HPK contained only 20% of the nephrons present in normal kidneys. The Cun and Ccr divided by GN (average values of single nephron Cun and Ccr) of HPK rats were about two and four times greater than normal levels, respectively. This hyperfiltration was not accompanied by systemic hypertension, but was associated with marked glomerular hypertrophy and glomerulosclerosis, which were observed mainly in the inner cortex. A considerable heterogeneity of glomerular size was found in HPK and most glomeruli of surface nephrons retained normal size and histology. A remarkable leakage of albumin into urine was found at 35 and 70 days of age. CONCLUSIONS: The HPK rat is a useful model for studying the pathophysiology of oligomeganephronic disease as well as glomerular hyperfiltration and hypertrophy induced by severe congenital reduction of nephrons.     

Renal osteopontin protein and mRNA upregulation during acute nephrotoxicity in the rat.

BACKGROUND: The effect of segment-specific proximal tubular injury on spatio-temporal osteopontin (OPN) distribution was determined in two different nephrotoxic rat models to evaluate its conceivability with a possible role for OPN in acute renal failure (ARF). OPN gene expression was further determined in proximal and distal tubular cells to investigate the origin of increased renal OPN. METHODS: Renal OPN protein and mRNA expression were compared in the rat during mercuric-chloride- vs gentamicin-induced ARF using immunohistochemistry and in situ hybridization. RESULTS: Mercuric chloride primarily induced tubular injury and subsequent cell proliferation in proximal straight tubules (PST), whereas gentamicin predominantly injured proximal convoluted tubules (PCT). In both models, the distribution of OPN protein was associated with increased OPN mRNA levels in proximal as well as distal tubular cells. However, upregulation was delayed in the proximal tubular segment suffering most from injury, i.e. PCT in gentamicin ARF vs PST in mercuric-chloride ARF. OPN immunostaining at the apical cell membrane from distal tubules was in contrast to perinuclear vesicular staining in proximal tubular cells. CONCLUSIONS: OPN gene and protein expression is induced in both proximal and distal tubular cells during rat toxic ARF. The distinct subcellular localization in proximal vs distal tubular cells indicates differences in OPN processing and/or handling. The spatio-temporal distribution is consistent with a possible role in renal injury and regeneration.     

Effect of low calcium and low phosphorus diets on the intestinal absorption of water in intact and parathyroidectomized pigs

Summary Young pigs, each surgically prepared beforehand with a Thiry-Vella loop of jejunum, were used to study the effect of feeding low calcium and low phosphorus diets on the intestinal absorption of water. Feeding a low phosphorus diet caused a highly significant stimulation in the absorption of water in parathyroid gland-intact and parathyroid-ectomized pigs; low calcium diets were without effect.     

氯化钴预处理对大鼠脂肪干细胞成脂及增殖的影响

目的观察脂肪来源问充质干细胞（ADSCs）在经氯化钴（CoCl2）预处理的条件下,其增殖、细胞状态变化以及成脂肪化倾向。方法通过有限稀释法分离、培养SD大鼠ADSCs,取第3代ADSCs,分别向骨细胞、脂肪细胞定向诱导分化鉴定,利用流式细胞仪检测大鼠ADSCs细胞表面标志物CD29,CD34,CIM4,CIM5的表达。将ADSCs经不同浓度CoCl2干预,利用Westernblot检测缺氧诱导因子1d（HIF-101）的表达情况。同时,利用MT＇F实验来检测大鼠ADSCs在不同浓度的CoCl2下细胞增殖的改变;并且通过油红O定量检测大鼠ADSCs在经历缺氧后的成脂情况。结果第3代ADSCs在倒置显微镜下观察,大多呈梭形,经流式鉴定,大鼠ADSCs细胞表面标志物CD29、CD44表达率高,而CD34、CD45表达率低,体外诱导培养的大鼠ADSCs能够向成骨细胞和成脂细胞分化,具有较高的自我更新能力。在MTr实验中,400、200ixmol／LCoCl2组,ADSCs增值减弱;而100、50Ixmol／LCoCl2的实验组,缺氧造成的对细胞增殖和细胞毒性与空白对照组相比,没有变化（P〉0．05）。HIF-1d的表达随着培养基中的CoCl2的浓度而增加。在光镜下观察发现,随着CoCl2浓度的升高以及时间的延长,大鼠ADSCs的成脂倾向越发明显（P〈0．001）。结论ADSCs在处于体外适量的CoCl2干预情况时,其增殖并不会受到影响,并且呈显著的增强其成脂倾向。     

Role of growth hormone in experimental phosphorus deprivation in the rat

Summary The demands of growth are known to exacerbate the effect of phosphorus deprivation (PD). We examined whether changes associated with PD could be prevented in young rats in which growth and growth hormone (GH) were eliminated by hypophysectomy (HPX) and whether PD in normal intact rats (INT) was associated with increased secretion of GH. INT or thyroxine- and ACTH-replaced HPX rats were fed one of the three diets: 0.31% P (NP); 0.027% P (LP), and 0.31% P, pair-fed with LP-mates (NP-PF). The results indicate that HPX did not qualitatively alter several physiologic responses to PD: (a) serum and urinary phosphorus (P) decreased and urinary calcium (Ca) increased; (b) net intestinal Ca retention fell and duodenal sac uptake of⁴⁵Ca rose; and (c) external P balance was restored and duodenal sac uptake of³²P-phosphate increased. Only the hypercalcemia seen in INT, LP rats was prevented by HPX. In INT rats serum immunoassayable GH levels, measured in single samples, were not different between different dietary groups while pituitary bioassayable GH was reduced in both LP and NP-PF rats when compared to the NP rats. Thus, except for hypercalcemia, the physiologic responses associated with PD are not prevented by the elimination of growth and GH, and the development of these responses in INT rats was not associated with a consistent or specific alteration in GH secretion. Deceased, November 30, 1979     

The intestinal handling of calcium by the rat in vivo,as affected by cortisol. Effect of dietary calcium supplements

Summary This paper reports the effects of cortisol on intestinal management of calcium and on related changes on bone metabolism. Five groups of 12 rats each fed a standard diet (0.8% Ca) received 2, 6, 16, 32, and 128 mg/kg/day of cortisol hemisuccinate, subcutaneously. After 16 days, intestinal absorption and excretion of Ca were measured with the aid of⁴⁵Ca. True Ca absorption increased as a function of dose up to 16 mg/kg/day and remained high with the larger doses. Endogenous fecal Ca excretion increased exponentially as a function of the dose from 16 mg/kg/day onwards. Therefore, a dual effect was observed: (a) an increase in true Ca absorption at low cortisol doses (which increased net Ca absorption); and (b) an increase in endogenous fecal Ca excretion at high doses (which reduced net Ca absorption). In no case was a depression of true Ca absorption observed.Growth rate and food conversion efficiency were depressed only with a cortisol dose of 128 mg/kg/day. The urinary excretion of hydroxyproline, pyrophosphate, and aminopolysaccharides decreased with low doses and increased above normal levels with the highest dose.When animals treated with 128 mg/kg/day of cortisol were fed Ca-enriched diets, net Ca absorption improved. Simultaneously, growth rate and food conversion efficiency approached normal values. In these experiments, net absorption of Ca was found to be inversely related to urinary excretion of hydroxyproline. The urinary rate of excretion of hydroxyproline is suggested as an indicator of the effect of a Ca supplement on cortisol affected connective tissue turnover.     

维持性血液透析患者钙磷代谢紊乱的影响因素及其与肾性贫血的相关性

目的调查我院血液透析中心患者钙磷代谢标志物血钙、血磷、全段甲状旁腺素(intact parathyroid hormone,iPTH)等指标的达标情况,探讨维持性血液透析患者钙磷代谢紊乱的影响因素及其与肾性贫血的关系,以便更好的控制钙磷代谢紊乱并管理贫血。方法研究纳入2010年1月至2015年1月在我院血液透析中心规律行血液透析(透析时间≥3个月)的终末期肾病患者作为研究对象,收集患者年龄、性别、透析时间、透析频率、残余尿量等相关资料及患者血钙、血磷、iPTH、血红蛋白(hemoglobin,Hb)等实验室检查指标,统计我院血液透析中心患者钙磷代谢标志物血钙、血磷、iPTH等各项指标的达标情况。然后分别根据年龄、透析龄、透析频率、残余尿量进行分组,比较各组间钙磷代谢指标的差异性,再分别根据血钙、血磷和iPTH进行分组,采用趋势卡方检验及方差分析比较各组间Hb达标情况。结果①本血液透析中心263例患者中,血钙达标率45.0%,血磷达标率40.1%,iPTH达标率23.7%,与透析预后与实践模式研究第4阶段(Dialysis Outcomes and Practice Pattern Study,DOPPS4)国家达标数据(56.0%、54.5%、32.1%)比较,达标率存在一定差距。②根据透析龄进行分组,透析龄≥3年组平均血钙水平显著高于透析龄3年组平均血钙水平;根据透析频率进行分组,每周2次透析组平均血钙水平显著高于每周≤2次透析组平均血钙水平,血磷水平显著低于每周≤2次透析组。根据残余尿量进行分组,有尿组(尿量≥100 rnl/24 h)钙磷乘积显著低于无尿组。根据年龄分组,年龄45岁组平均血磷水平、iPTH水平、钙磷乘积水平显著低于年龄≤45岁组。③将血钙浓度分为2.1 mmol/L、2.1~2.5 mmol/L、2.5 mmol/L三组。随着血钙增高,Hb达标(≥110 g/L)人数占比越来越大,由38.8%上升至64%,差异有统计学意义(P0.05)。将血磷浓度分为1.13 mmol/L、1.13~1.78 mmol/L、1.78 mmol/L三组,随着血磷增高,Hb达标(110 g/L)人数占比越来越大,由31%上升至53.4%,差异有统计学意义(P0.05)。将血iPTH浓度分为150 ng/L、150~300 ng/L、300 ng/L三组。随着iPTH增高,Hb达标(≥110 g/L)人数占比越来越小,由52.8%下降至36.8%,差异有统计学意义(P0.05)。结论①适当增加透析频率及有效保护残余尿量有助于控制及改善钙磷代谢紊乱。②血钙、血磷浓度上升,有利于维持性血液透析患者Hb的达标。血iPTH浓度上升,不利于维持性血液透析患者Hb的达标。     

血清钙磷乘积预测老年椎体压缩性骨折风险的意义

目的 研究血清钙磷乘积能否作为预测骨质疏松性椎体压缩性骨折（osteoporotic vertebral compression fracture, OVCF）发病危险性的血清学指标。方法 本研究随机纳入我院2015年8月至2021年4月老年人OVCF患者200名为观察组和同期行因股骨头坏死或骨关节炎行髋、膝关节置换术的患者200名为对照组，收集两组患者的年龄、性别、既往病史(高血压、糖尿病)、入院时初次生化指标主要包括白蛋白、尿素氮、血清肌酐、血清钙、血清磷数值等，并进行统计学分析。结果 观察组白蛋白、血清钙、血清磷、钙磷乘积、校正血钙、校正钙磷乘积均低于对照组，差异有统计学意义（P < 0.05）。经多因素Logistic回归分析显示低数值的血清钙、血清磷、钙磷乘积、校正血钙、校正钙磷乘积均能作为OVCF患者的危险因素。同时，通过绘制ROC曲线得出钙磷乘积、校正钙磷乘积预测骨质疏松性椎体压缩性骨折发病风险的效果良好。其中，钙磷乘积预测效果最佳，对应临界值为29.88，灵敏度0.72，特异性0.62；其次为校正钙磷乘积，对应临界值为30.50，灵敏度0.74，特异性0.62。结论 钙磷乘积及校正钙磷乘积可以作为预测老年人OVCF发病危险性的血清学指标。针对这项危险因素可以早期进行临床干预以进一步降低OVCF的发生风险。     

补肾化痰方对去势骨质疏松大鼠钙沉积的影响

目的观察补肾化痰方对去势骨质疏松大鼠钙沉积的影响。方法 6月龄SD大鼠40只,随机分为4组,每组10只,即假手术组、模型组、补肾化痰组和补肾组。采用micro CT检测大鼠的骨密度((bone mineral density,BMD),酶联免疫吸附法(enzyme linked immunosorbent assay,ELISA)检测血清胎球蛋白(fetuin-A)、基质gla蛋白(matrix gla protein,MGP)水平,蛋白质印迹法(Western blot,WB)检测骨组织Fetuin-A、MGP蛋白的表达,免疫组化(immunohistochemical,IHC)检测其定位。结果与假手术组相比,模型组、补肾化痰组及补肾组的BMD均降低,血清Fetuin-A、MGP水平及骨组织Fetuin-A水平均降低,骨组织MGP水平升高,差异有统计学意义(P0.001);与模型组相比,补肾化痰组及补肾组的BMD均升高,血清Fetuin-A、MGP水平及骨组织Fetuin-A水平均升高,而骨组织MGP水平降低,差异有统计学意义(P0.001);补肾化痰组与补肾组相比较,补肾化痰组血清Fetuin-A、MGP水平升高明显,差异有统计学意义(P0.001),而两组的BMD、骨组织Fetuin-A、MGP含量则没有明显的差异(P0.05)。结论补肾化痰方能够影响血清胎球蛋白-基质gla蛋白-钙磷矿化复合物的形成,从而改善钙沉积,促进骨矿化,起到防治骨质疏松的作用。